Call for new guideline adoption to get medicines to patients faster

Complex Innovative Design (CID) trials could be transformed for the better, following the publication of recommendations, published in the British Journal of Cancer. The authors believe, if implemented, the ten recommendations they’ve developed for CID trials could ultimately reduce the time it takes to get innovative treatments to patients with cancer.

Experts are now calling on clinicians, funders, regulators and the pharmaceutical industry to get behind the recommendations and work together to rapidly implement them. CID trials are increasingly being used as an evaluation method by researchers, instead of traditional drug development pathways involving clinical trials from phases 1 to 4.

The CID approach enables researchers to carry out more complex trials that address multiple clinical questions at once. For example, a drug can be simultaneously evaluated for safety and efficacy with different cancer types, which can change as the trial progresses, accelerating the traditional route to drug licencing.

However, they can be challenging to conduct and there are currently no practical guidelines for teams that fund, design and conduct these trials in Europe.

The Experimental Cancer Medicine Centre (ECMC) network, funded by Cancer Research UK, the National Institute for Health Research (NIHR) and the health departments in Scotland, Wales and Northern Ireland convened a working group of academics, funders, regulators, pharmaceutical industry representatives and patients to address this challenge.

They have developed ten key recommendations to cover each stage of the clinical trial pathway:

1. Trial Planning and Design - Engagement with Regulators: Investigators/sponsors should arrange a joint meeting with regulators, HTA bodies and other key stakeholders as early as possible before or during the trial design to guide and shape the delivery of the CID trial, especially if accelerated (e.g. conditional) approval is likely to be applied for.

2. Protocol Development: The protocol should identify and briefly describe any possible future modifications (such as additional study arms) to reduce the likelihood of substantial amendments. Events defining the end of trial must be included.  

3. Patients and public involvement (PPI): Patients and the public may require specific training, support, and perhaps also accreditation, in order to review and/or manage CID trials. 

4. Patient Facing Documentation: A practical approach using three-part patient information should be provided; comprising an invitation document, a study arm-specific document and a handbook. Multimedia can be considered for some or all of these documents.

5. Statistical Considerations: Experienced and detailed statistical input is required to provide an over-arching statistical design with flexibility to incorporate individual variations for different treatments, diseases and molecular characteristics. Having a range of expertise within the oversight committee will ensure timely and appropriate responses to the frequent analyses produced.

6. Defining Leadership and Oversight: A Trial Management Group with experience of CID trials should be convened to oversee the study. New Chief Investigators (CIs) and/or Principal Investigators (PIs) should be appointed during the study as its requirements evolve. 

7. Dissemination of Results: When a research question is answered, or a study arm is completed, timely reporting of trial data at these pre-specified time-points should be supported as best practice.

8. Staff Training: Training in complex trial methodologies should be included in the undergraduate and post-graduate training curricula of relevant health care professionals in order to ensure appropriate resources are in place to deliver CID trials.

9. Approval and Reimbursement Decisions: Accelerated access initiatives are vital in ensuring CID trial findings are rapidly transitioned to regulatory approval, reimbursement decisions and adoption into clinical practice.

10. Evaluating the impact on public health: Impact analyses should be conducted on all CID trials to ensure they deliver on their promise to provide timely access to these medicines in clinical practice without compromising patient safety.

Taken together, these recommendations could improve the conduct, quality and acceptability of oncology CID trials in clinical research. Furthermore, improving how different stakeholders interact, promote and share their learnings from CID studies, say the authors, will foster a clinical research environment that could enable CID trials to be carried out in a range of new clinical areas.

Professor Pam Kearns, director of the Cancer Research UK clinical trials unit at the University of Birmingham and co-author of the paper, said: “We owe it to our patients to bring potentially more effective novel treatments into the clinic as quickly as possible, and these recommendations will ensure we have good quality CID trials in place to deliver this promise.” 

References

Blagden, S. P., et al. (2020) Effective delivery of Complex Innovative Design (CID) cancer trials – A consensus statement. British Journal of Cancer. DOI: 10.1038/s41416-019-0653-9